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The FDA Inspection and Enforcement Process: A Guide for HCT/P Manufacturers and Providers

stem cell therapyBy: Matthew Fischer

In November 2017, the U.S. Food and Drug Administration (FDA) issued new guidance regarding its current interpretation of the minimal manipulation and homologous use criteria set forth in 21 CFR Part 1271(a) and the agency’s view on the same surgical procedure exception under 21 CFR 1271.15(b).  Additionally, the FDA issued a notice to all interested stakeholders that the agency intends to initiate increased discretionary enforcement over the next 36 months for HCT/P businesses.  Based on the agency’s latest position, it is important for HCT/P manufacturers and providers to understand the inspection process and be prepared to respond accordingly in this heightened regulatory environment.

The FDA is tasked with regulating HCT/Ps under the authority of Section 361 of the Public Health Service Act (PHS).  Within the FDA, the Center for Biologics Evaluation and Research (CBER) is responsible for ensuring the safety of these products and promoting corrective action.  In order to reach this goal, CBER is armed with an array of administrative actions to address violations of regulatory significance.  

Inspections and FDA Form 483

There are no specific guidelines regarding inspection frequency.  According to the FDA Compliance Program Guidance Manual for HCT/Ps, divisions must decide which companies to inspect based on resources they have been allotted and risk-based selection priorities.  When an inspection does occur, an investigator will issue a FDA Form 483 at the conclusion of the inspection.  This form will set forth all observed conditions that in their judgment may constitute violations.  The form, however, does not constitute a final agency determination of whether the conditions are in fact a violation.  The findings are essentially considered along with other collected information to determine whether additional action is needed.  A response is not required but recommended.  Also in the response, a corrective action should be included in order to fully satisfy the agency’s concerns.

Warning and Untitled Letters

If a manufacturer’s or provider’s response following an inspection is found to be inadequate and the violations are seen as significant, the next action taken by the agency is the service of a warning letter.  A warning letter is one of the agency’s primary means of attaining compliance.  This type of letter is advisory in nature but requires a written response within 15 days of receipt to address corrective action taken.  These letters are posted on the agency’s website.  In contrast, if an issue is found but not seen as of regulatory significance, the agency may issue an “untitled letter” addressing the agency’s concerns that need further attention.  These letters do not require a response and are not posted online.

Order of Retention, Recall, and/or Destruction

Failure to promptly correct deviations following the issuance of a warning letter can result in further regulatory action.  FDA regulations permit the agency to order retention, recall, and/or destruction if the agency determines that it must act to prevent the distribution of a HCT/P that may result in the introduction or spread of a communicable disease.  For the agency to take action the deviations must be well documented.  To challenge, the regulations permit a manufacturer or provider to request a hearing within 5 working days of receipt of an order.  If a hearing is requested, the order is placed in abeyance.

In light of the new realities that HCT/P manufacturers and providers face, all businesses must prepare for inspectors to appear at their reception desks, ask questions, and request documents.  If negative correspondence is received from the agency, the critical first step is retaining competent counsel to prevent crushing publicity, insolvency, and/or prosecution.